Simulated microgravity exposure markedly attenuates the baroreflex total loop gain and induces orthostatic hypotension in male rats

Autonomic dysfunction is recognized as the central mechanism of orthostatic hypotension after microgravity exposure. Because the arterial baroreflex regulates arterial pressure (AP) via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function under simulated microgravity by conducting an open-loop analysis. We used Sprague-Dawley rats after hindlimb unloading (HU) for 2 weeks. We isolated the carotid sinuses from the systemic circulation, then changed intracarotid sinus pressure (CSP) stepwise and recorded SNA and AP responses. We compared CSP-AP (total loop), CSP-SNA (mechanoneural arc), and SNA-AP (neuromechanical arc) relations between control rats (n = 9) and HU rats (n = 7). The total loop gain at the operating point decreased significantly in HU rats compared with control rats (0.3 ± 0.4 vs. 1.1 ± 0.4 mmHg/mmHg, p < 0.05). In addition to the decrease in the mechanoneural arc gain at the operating point, the neuromechanical arc gain also decreased significantly in HU rats compared with control rats. A numerical simulation experiment showed a greater AP fall with a significant reduction of the total loop gain in response to hypotensive stress in HU rats. Thus, we conclude that simulated microgravity impairs baroreflex sympathetic regulation in the lower AP range, which may play an important role in the pathogenesis of orthostatic hypotension after microgravity exposure.